title: Thrombospondin-1-induced smooth muscle cell chemotaxis and proliferation are dependent on transforming growth factor-β2 and hyaluronic acid synthase.
abstract: Angioplasty causes local vascular injury, leading to the release of thrombospondin-1 (TSP-1), which stimulates vascular smooth muscle cell (VSMC) migration and proliferation, important steps in the development of intimal hyperplasia. Transforming growth factor beta 2 (TGF-β2) and hyaluronic acid synthase (HAS) are two pro-stenotic genes upregulated in VSMCs by TSP-1. We hypothesized that inhibition of TGF-β2 or HAS would inhibit TSP-1-induced VSMC migration, proliferation, and TSP-1 signaling. Our data demonstrate that Inhibition of either TGF-β2 or HAS inhibited TSP-1-induced VSMC migration and proliferation. Activation of ERK 1 was decreased by TGF-β2 inhibition and unaffected by HAS inhibition. TGF-β2 and HAS are not implicated in TSP-1-induced thbs1 expression, while they are each implicated in TSP-1-induced expression of their own gene. In summary, TSP-1-induced VSMC migration and proliferation rely on intact TGF-β2 signaling and HAS function. TSP-1 activation of ERK 1 is dependent on TGF-β2. These data further expand our understanding of the complexity of TSP-1 cellular signaling and the involvement of TGF-β2 and HAS.
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY, 13210, USA, steinje@upstate.edu.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Stein
authors.forename: Chinenye
authors.initials: C
authors.lastname: Iwuchukwu
authors.forename: Kristopher G
authors.initials: KG
authors.lastname: Maier
authors.forename: Vivian
authors.initials: V
authors.lastname: Gahtan
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects; D015550:Cell Degranulation; D049109:Cell Proliferation; D002633:Chemotaxis / Q000502:physiology*; D004789:Enzyme Activation; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D000076002:Hyaluronan Synthases; D006923:Hymecromone / Q000494:pharmacology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D019700:Thrombospondin 1 / Q000378:metabolism*; D053781:Transforming Growth Factor beta2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D057772:Vascular System Injuries / Q000378:metabolism
chemical_list: D019700:Thrombospondin 1; D053781:Transforming Growth Factor beta2; D006923:Hymecromone; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; D048052:Mitogen-Activated Protein Kinase 3